Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

Abstract

Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

The placenta: a multifaceted, transient organ

“…One benefit is that it is more freely permeable to hydrophilic solutes, which are thought to pass through water-filled transtrophoblastic channels. Although the great apes also share haemochorial placentation, trophoblast invasion is deepest in the human [87]. This is consistent with the theory that greater access to the maternal blood supply facilitates growth of our large fetal brain [88].…”

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

“…1 and 6, fetal invasion in humans and other apes is extremely invasive (referred to as interstitial invasion). Fetal placental cells invade the ape uterus via endovascular and interstitial routes, in contrast to most other mammals, including monkeys, in which migration of fetal cells mainly occurs in arteries (27). Interstitial invasion allows the ape fetus to remodel maternal vasculature more extensively than monkeys and other mammals (27,28).…”

“…It is interesting to note, however, that the receptor-ligand interaction that allows uNKs to inhibit placental cells also evolved in the stem lineage of apes. HLA-C molecules on placental cells, and the lineage of KIR genes expressed by uNKs that recognize HLA-C, are only present in the great apes and not in monkeys or more basal primates (12,27). Thus, one maternal response to increased aggressiveness of the ape placenta may have been the inhibition of placental cells by uNK cells.…”

“…Groups with an asterisk are those from which prolactin promoter reporter constructs were made in this study. a Carter (27) reports that orangutan specimens were not available to determine whether orangutan invasion proceeds through the interstitial route, but Mossman (38), Benirschke (39), and Gruenwald (28) describe fetal invasion in orangutans as interstitial and/or very invasive. b There is some evidence for interstitial invasion in rats during the last part of pregnancy (40).…”

Placental Evolution within the Supraordinal Clades of Eutheria with the Perspective of Alternative Animal Models for Human Placentation

“…Among 2 Advances in Biology them are nonmurine rodents native to South America and Africa [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], as was shown by Figure 2, bats [41][42][43], anteaters and armadillos [44,45], and some other taxa [46][47][48][49][50][51]. Also, there were several promising attempts to reinvestigate historical histological material from museum collections such as neotropical primates [52] or great apes [53][54][55][56] in order to answer open questions.…”